Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptome profile of mouse lung dendritic cell subsets and macrophages.

ABSTRACT: Dendritic cell (DC) are critical initiators and regulators of immunity to pathogens, vaccines, tumors and tolerance to self. Mouse and human dendritic cells (DCs) are comprised of functionally specialized subsets, but precise interspecies correlation is currently incomplete and hampers the full translation of murine findings to human DC-based clinical therapies. In this study, we show that murine lung and gut lamina propria CD11b+ DC populations are comprised of two subsets: FLT3- and IRF4-dependent CD24+CD64- DCs and contaminating CSF-1R-dependent CD24-CD64+ macrophages. CD11b+CD24+CD64- DCs are instrumental in inducing Th17 cell immune response in the steady state and upon Aspergillus fumigatus challenge. We also identified human CD1c+CD11b+ DCs as the functional homologue of mouse mucosal CD11b+ DCs. Our findings highlight the conservation of key immune functions across species and aid the translation of murine studies to human DC immunobiology. The data for the associated human studies have been stored within GSE35459. Gene Expression from total RNA from specific mouse dendritic cell subsets purified by FACS

ORGANISM(S): Mus musculus

SUBMITTER: Pavandip Singh Wasan

PROVIDER: E-GEOD-46680 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses.

Schlitzer Andreas A McGovern Naomi N Teo Pearline P Zelante Teresa T Atarashi Koji K Low Donovan D Ho Adrian W S AW See Peter P Shin Amanda A Wasan Pavandip Singh PS Hoeffel Guillaume G Malleret Benoit B Heiseke Alexander A Chew Samantha S Jardine Laura L Purvis Harriet A HA Hilkens Catharien M U CM Tam John J Poidinger Michael M Stanley E Richard ER Krug Anne B AB Renia Laurent L Sivasankar Baalasubramanian B Ng Lai Guan LG Collin Matthew M Ricciardi-Castagnoli Paola P Honda Kenya K Haniffa Muzlifah M Ginhoux Florent F

Immunity 20130501 5

Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24(+)CD64(-) DCs and contaminating CSF-1R-dependent CD24(-)CD64(+) macrophages. Functionally, loss of CD24(+)CD11b(+) DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after A ...[more]

PMID: 23706669

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Project description:Dendritic cells (DCs) are a complex group of cells which play a critical role in vertebrate immunity. Spleen or lymph node resident DCs are subdivided into conventional DC (cDC) subsets (CD11b and CD8alpha in mouse; BDCA1 and BDCA3 in man) and plasmacytoid DCs (pDCs). It is currently unclear if these various DC populations belong to a unique hematopoietic lineage and if the subsets identified in the mouse and human systems are evolutionary homologs. To bring novel insights into these questions, we sought conserved genetic signatures for these DCs through the analysis of a compendium of genome-wide expression profiles of mouse or human leukocytes. We show through clustering analysis that all spleen resident DC subsets form a distinct branch within the leukocyte family tree, and reveal a transcriptomal signature evolutionary conserved in all these DC subsets. Moreover we identify a large gene expression program shared between mouse and human plasmacytoid DCs, and smaller conserved profiles shared between mouse and human cDC subsets. Finally, we use compendium analysis to re-evaluate the classification of interferon-producing killer DCs (IKDCs) and lin-CD16+HLA-DR+ cells, which have both been claimed to be DCs, and show that these cells are more closely linked to NK or myeloid cells, respectively. Our study thus provides a unique resource for future investigation of the evolutionarily conserved molecular pathways governing the ontogeny and functions of leukocyte subsets, especially DCs. Experiment Overall Design: This study includes data from cell sort purified dendritic cells, B cells, NK cells, and CD8 T cells. 2 or 3 independent replicates were made for each cell type. The genearray was performed in an attempt to investigate the relationships between DCs subsets and with other leukocytes, in mouse, in human, and between these 2 species. To this end, public data for mouse CD4 T cells and macrophages, as well as public data for human leukocyte subsets were also used in the analysis. The results have led to the identification of specific transcriptional programs conserved between human and mouse dendritic cell subsets.

Dataset Information

Transcriptome profile of mouse lung dendritic cell subsets and macrophages.

Publications

IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses.

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